Cox10 Knockout mouse models

Heme A biosynthesis begins with Cox10, the mouse ortholog of human COX10, which encodes the inner membrane heme A farnesyltransferase that converts protoheme, or heme B, into heme O by farnesylating a vinyl side chain, the committed first step toward the heme A cofactors of cytochrome c oxidase. Without heme A, subunit MT-CO1 cannot mature, so complex IV assembly stalls and the enzyme is degraded, producing isolated cytochrome c oxidase deficiency. Human COX10 mutations cause Leigh syndrome, leukodystrophy with tubulopathy, and fatal infantile encephalomyopathy, and conditional mouse alleles have been used productively to generate muscle and neuron restricted complex IV deficiency. Design accordingly: a floxed conditional null builds tissue specific COX deficiency models, while hypomorphic knockins reproduce partial cofactor synthesis. No paralog performs this farnesylation. Pair Ckmm-Cre, Nes-Cre, or Camk2a-Cre with COX and SDH histochemistry, spectrophotometric complex IV activity, and blue native assembly analysis.

Whole body loss of Cox10 gives the clearest readout when the question is whether the gene is required at all. Follow up tissue work can still move to a conditional allele if lethality or compensation appears.